Translatomics for sORF, micropeptide and tRNA
Recent Publications Harnessing the Power of Translatomics
Every week we provide a digest of a small number of recent interesting papers in the field of translatomics.
In this week’s Sunday papers,
- Yang et al. combine ribo-seq and proteomics to distinguish translated and stable functional peptides.
- Cao et al. reveal hidden translational suppression of meiosis genes, identifies uORF-mediated regulation, and detects novel micropeptides.
- Dong et al. show that increasing cognate tRNAs reduces stalling at non-optimal codons, directly linking tRNA modification to improved translation dynamics and protein output.
Proteogenomics-enabled discovery of novel small open reading frame (sORF)-encoded polypeptides in human and mouse tissues
Nucleic Acids Research. 2025.
Yang, M., Xie, Y., Wang, L., Jungreis, I., Ou, T., Kellis, M., Wang, J. and Zhu, Y
Yang et al. present a proteogenomics framework that mines large-scale public mass spectrometry datasets from diverse human and mouse tissues to identify small open reading frame (sORF)-encoded polypeptides (SEPs).
By searching proteomics data against databases supplemented with sORF annotations and then using ribosome profiling and conservation analyses as supporting evidence, the authors identify hundreds of previously unannotated sORFs in both species, including many with tissue-selective expression patterns. They show that many detected sORFs are very short and often use non-ATG start codons, underscoring the complexity of the previously underexplored microproteome.
The study also highlights conserved candidates with likely biological relevance, such as sORFs in HNRNPUL2 and Tug1, and introduces a scalable filtering and validation workflow for future sORF discovery.
Learn more about EIRNABio’s ribosome profiling services here.
Comparative Analysis of Testicular Transcriptional and Translational Landscapes in Yak and Cattle–Yak: Implications for Hybrid Male Sterility
Biomolecules. 2025.
Cao, M., Guo, S., Ding, Z., Hu, L., Xiong, L., Ge, Q., Pei, J. and Guo, X
Cao et al. compares transcriptional (RNA-seq) and translational (Ribo-seq) landscapes in yak and sterile cattle–yak testes to uncover mechanisms of hybrid male sterility. It shows that gene expression is often uncoupled between mRNA and translation, highlighting the importance of post-transcriptional regulation.
The authors identify over 4,000 genes with altered translation efficiency, with widespread translational downregulation of spermatogenesis-related genes in cattle–yak.
Critically, key meiotic genes including MEIOB, MEI1, and SMC1B are reduced at the translation level only, despite unchanged mRNA levels, implicating translational defects in infertility.
They also characterize upstream open reading frames (uORFs) and discover novel small polypeptides, suggesting additional regulatory layers in testicular function. Overall, Ribo-seq in this study reveals that translational dysregulation, which especially affects meiosis, contributes to impaired spermatogenesis in cattle–yak hybrids.
Learn more about EIRNABio’s ribosome profiling services here.
Chemically modified tRNA enhances the translation capacity of mRNA rich in cognate codons
Nature Communications. 2025
Dong, L., Wang, J. and Xia, Q
Dong et al. describe a tRNA-plus strategy to enhance translation by modulating tRNA availability and modification. Using SARS-CoV-2 Spike mRNA as the main model, they show that overexpression of selected cognate tRNAs increases mRNA stability and translation efficiency, boosting protein output by up to 4.7-fold. They also engineer chemically synthesized tRNAs with site-specific modifications, particularly in the anticodon loop and TΨC loop, which show about 4-fold higher decoding efficacy, greater stability, and reduced immunotoxicity compared with unmodified tRNAs.
When co-delivered with Spike mRNA in lipid nanoparticles, these tRNAs increase protein production and enhance humoral and cellular immune responses in vivo. The study further suggests that tRNA-plus can complement codon optimization, supporting a new way to improve mRNA therapeutics and vaccines.